US11584736B2ActiveUtilityA1
Heterocyclic P2Y14 receptor antagonists
Est. expiryFeb 9, 2038(~11.6 yrs left)· nominal 20-yr term from priority
C07D 211/70A61P 11/06A61P 29/00C07D 409/10C07D 235/18C07D 211/18C07D 471/08C07D 209/10C07D 249/06C07D 209/20C07D 401/10A61P 13/12C07D 401/14C07D 211/34C07C 235/84C07D 403/04
67
PatentIndex Score
1
Cited by
46
References
25
Claims
Abstract
Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2Y14R receptor agonist in a mammal in need thereof, wherein R1-R8, X, Y, Z, X′, Y′, Z′, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A compound of formula (I):
wherein (i) X is N, Y is CH, and Z is CH, (ii) X is CH, Y is N, and Z is CH, (iii) X is CH, Y is CH, and Z is N, or (iv) X, Y, and Z are all CH,
R 1 is trifluoromethylphenyl,
R 2 is COOH, CN, CONH 2 , or
A is selected from the group consisting of
wherein R 3 is at each occurrence H, C 1 -C 10 alkyl, C 3 -C 10 alkynyl, benzyl, C 1 -C 6 alkoxycarbonyl, CO((CH 2 ) 2 O) 6 (CH 2 ) 2 Q wherein Q is NH 2 , NHCOCH 3 , or NHCO(CH 3 ) 3 , or CO((CH 2 ) 2 O) 6 CH 3 , and wherein R 4 and R 5 are each H or F,
with the proviso that the compound is not 4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalene-carboxylic acid,
or a pharmacologically acceptable salt thereof.
2. The compound or salt of claim 1 , wherein X, Y, and Z are all CH.
3. The compound or salt of claim 1 , wherein A is
4. The compound or salt of claim 3 , wherein the compound is selected from the group consisting of:
5. A pharmaceutical composition comprising a compound or salt of claim 1 and a pharmaceutically acceptable carrier.
6. A method for antagonizing a P2Y 14 R receptor in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 1 .
7. A method for treating an inflammatory condition in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 1 .
8. The method of claim 7 , wherein the inflammatory condition is selected from the group consisting of asthma, cystic fibrosis, and sterile inflammation of the kidney.
9. A compound of formula (III), (IV), or (V):
wherein R 6 is selected from the group consisting of
R 7 is COOH, CONH 2 , CN
or COCH 2 NMe 2 ,
R 8 is selected from the group consisting of C 1 -C 10 alkyl, —CONHR 12 R 13 , —CONH(CH 2 ) m —NHR 14 R 15 ,
R 10 is halo or CF 3 ,
R 11 is halo, OH, or C 1 -C 6 alkoxy,
R 12 and R 13 are independently H or C 1 -C 6 alkyl,
R 14 and R 15 are independently H or C 1 -C 6 alkyl,
R 16 is H, C 1 -C 10 alkyl, or C 3 -C 10 alkynyl,
R 17 and R 18 are both H or both F, and
m is an integer of from 1 to about 10,
(i) X is N, Y is CH, and Z is CH, (ii) X is CH, Y is N, and Z is CH, (iii) X is CH, Y is CH, and Z is N, or X, Y, and Z are all H,
X′ and Y′ are C or N, and
Z′ is N or CR 9 wherein R 9 is H or C 1 -C 6 alkyl,
or a pharmaceutically acceptable salt thereof;
with the proviso that, in the compound of formula (III), when X=N and Y and Z are
CH, R 7 is CN, and R 6 is
wherein R 10 is CF 3 , then R 8 is not C 6 alkyl.
10. The compound or salt of claim 9 , wherein R 7 is COOH.
11. The compound or salt of claim 9 , wherein the compound is
12. The compound or salt of claim 9 , wherein the compound is
13. The compound or salt of claim 9 , wherein the compound is
or
14. A pharmaceutical composition comprising a compound or salt of claim 9 and a pharmaceutically acceptable carrier.
15. A method for antagonizing a P2Y 14 R receptor in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 9 .
16. A method for treating an inflammatory condition in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 9 .
17. The method of claim 16 , wherein the inflammatory condition is selected from the group consisting of asthma, cystic fibrosis, and sterile inflammation of the kidney.
18. A compound of formula (II):
wherein R 6 is selected from the group consisting of
R 7 is COOH, CONH 2 , CN
or COCH 2 NMe 2 ,
R 8 is selected from the group consisting of C 2 -C 10 alkyl, —CONHR 12 R 13 , —CONH(CH 2 ) m —NHR 14 R 15 ,
wherein:
R 10 is halo or CF 3 ,
R 11 is halo, OH, or C 1 -C 6 alkoxy,
R 12 and R 13 are independently H or C 1 -C 6 alkyl,
R 14 and R 15 are independently H or C 1 -C 6 alkyl,
R 16 is H, C 1 -C 10 alkyl, or C 3 -C 10 alkynyl,
R 17 and R 18 are both H or both F,
m is an integer of from 1 to about 10,
X′ and Y′ are C or N, and
Z′ is N or CR 9 wherein R 9 is H or C 1 -C 6 alkyl,
with the proviso that when R 6 is 4-chlorophenyl, R 7 is COOH, and R 9 is CH, then R 8 is not alkyl;
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising a compound or salt of claim 18 and a pharmaceutically acceptable carrier.
20. A method for antagonizing a P2Y 14 R receptor in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 18 .
21. The compound or salt of claim 9 , wherein the compound is a compound of formula (III) and wherein R 7 is COOH, CONH 2
or COCH 2 NMe 2 .
22. A pharmaceutical composition comprising a compound or salt of claim 21 and a pharmaceutically acceptable carrier.
23. A method for antagonizing a P2Y 14 R receptor in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 21 .
24. A method for treating an inflammatory condition in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound or salt of claim 21 .
25. The method of claim 24 , wherein the inflammatory condition is selected from the group consisting of asthma, cystic fibrosis, and sterile inflammation of the kidney.Cited by (0)
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